An open-label, controlled, multi-site, interventional, 2-arm, Phase II/III trial of BNT113 in combination with pembrolizumab vs pembrolizumab monotherapy as first line treatment in patients with unresectable recurrent or metastatic HPV16+ HNSCC expressing programmed cell death ligand-1 (PD-L1) with combined positive score (CPS) ≥1. This trial has two parts. Part A, is an initial non-randomized Safety Run-In Phase to confirm the safety and tolerability at the selected dose range level of BNT113 in combination with pembrolizumab. Part B, is a randomized part to generate pivotal efficacy and safety data of BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy in the first line setting in patients with unresectable recurrent or metastatic HPV16+ HNSCC expressing PD-L1 with CPS ≥1. Patients included in the Safety Run-In Phase of the trial (Part A) will not be randomized to Part B and will continue on-trial treatment (BNT113 plus pembrolizumab) within Part A. For Part B, an optional pre-screening phase is available for all patients where patients' tumor samples may be submitted for central HPV16 DNA and central PD-L1 expression testing prior to screening into the main trial. Patients will be treated with BNT113 in combination with pembrolizumab or with pembrolizumab monotherapy for approximately up to 24 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
350
IV injection
IV infusion
California Research Institute
Los Angeles, California, United States
WITHDRAWNUCLA Cancer Care
Los Angeles, California, United States
RECRUITINGStanford Cancer Institute
Palo Alto, California, United States
COMPLETEDYale University
New Haven, Connecticut, United States
Part A - Occurrence of treatment-emergent adverse event (TEAE) - BNT113 in combination with pembrolizumab
TEAE assessed according to Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) including Grade ≥3, serious, and fatal TEAEs, by relationship.
Time frame: up to 27 months
Part B - Overall survival (OS)
OS defined as the time from randomization to death from any cause.
Time frame: up to 48 months
Part B - Progression-free survival (PFS)
PFS defined as the time from randomization to the first objective tumor progression (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\] assessed by the blinded independent central review \[BICR\]), or death from any cause, whichever occurs first.
Time frame: up to 48 months
Part A and B - Overall response rate (ORR)
ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR) (per RECIST 1.1 assessed by BICR and investigator) is observed as best overall response.
Time frame: up to 48 months
Part A and B - Duration of response (DOR)
DOR defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (progressive disease \[PD\] per RECIST 1.1) or death from any cause, whichever occurs first. In Part A, assessment will be done by both BICR and investigator; in Part B, only by BICR.
Time frame: up to 48 months
Part A - Disease control rate (DCR)
DCR defined as the proportion of patients in whom a CR or PR or stable disease (SD) (per RECIST 1.1, assessed at least 6 weeks after first dose by BICR and investigator) is observed as best overall response.
Time frame: up to 48 months
Part B - Progression free survival (PFS)
PFS defined as the time from randomization to the first objective tumor progression (per RECIST 1.1 by investigator's assessment) or death from any cause, whichever occurs first.
Time frame: up to 48 months
Part B - PFS rate at 6 months
Defined as the proportion of patients without objective tumor progression (per RECIST 1.1 assessed by BICR and investigator) or death from any cause
Time frame: from randomization until 6 months after randomization
Part B - PFS rate at 12 months
Defined as the proportion of patients without objective tumor progression (per RECIST 1.1 assessed by BICR and investigator) or death from any cause.
Time frame: from randomization until 12 months after randomization
Part B - Occurrence of TEAEs - BNT113 in combination with pembrolizumab compared to pembrolizumab monotherapy
TEAEs assessed according to CTCAE v5.0 including Grade ≥3, serious, and fatal TEAEs by relationship.
Time frame: up to 27 months
Part B - Occurrence of dose reduction, delay, and discontinuation of trial treatments due to TEAEs
BNT113 in combination with pembrolizumab compared to pembrolizumab monotherapy.
Time frame: up to 27 months
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The George Washington Cancer Center
Washington D.C., District of Columbia, United States
RECRUITINGUniversity of Miami Miller School of Medicine
Miami, Florida, United States
RECRUITINGUniversity Cancer and Blood Center
Athens, Georgia, United States
WITHDRAWNWinship Cancer Institute
Atlanta, Georgia, United States
RECRUITINGNorton Cancer Institute
Louisville, Kentucky, United States
RECRUITINGTufts Medical Center
Boston, Massachusetts, United States
RECRUITING...and 179 more locations